Analysis of variation in the melanocortin‐4 receptor gene (mc4r) in golden retriever dogs

Berg, Linda van den; Berg, Stéphanie Martine van den; Martens, Ellen; Hazewinkel, H. A. W.; Dijkshoorn, N. A.; Waal, Henriëtte A. Delemarre-van de; Heutink, Peter; Leegwater, P.A.J.; Heuven, H.C.M.

doi:10.1111/j.1365-2052.2010.02049.x

Cited by 20 publications

(13 citation statements)

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“…It indicated that silent mutation of MC4R genes in female dogs could affect the modulation of canine body weight, and the estrogen could be an important effective factor of MC4R function to regulate body weight of Beagle dogs. Recently, some SNPs of canine MC4R gene, such as G637T, T777C and C+33G, were found from 19 different dog breeds [16, 18]. For the SNPs G637T and T777C, no association of the variant with canine body weight, length, height, or body index score was found in 187 Golden Retrievers [18].…”

Section: Resultsmentioning

confidence: 99%

“…Recently, some SNPs of canine MC4R gene, such as G637T, T777C and C+33G, were found from 19 different dog breeds [16, 18]. For the SNPs G637T and T777C, no association of the variant with canine body weight, length, height, or body index score was found in 187 Golden Retrievers [18]. However, the associations between polymorphisms of MC4R with obesity factors [10, 15], and birth weight [17] have been verified in other animals.…”

Section: Resultsmentioning

confidence: 99%

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The SNPs of Melanocortin 4 Receptor (MC4R) Associated with Body Weight in Beagle Dogs

Zeng

Zhang

2014

Exp. Anim.

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Melanocortin 4 receptor (MC4R), which is associated with inherited human obesity, is involoved in food intake and body weight of mammals. To study the relationships between MC4R gene polymorphism and body weight in Beagle dogs, we detected and compared the nucleotide sequence of the whole coding region and 3′- and 5′- flanking regions of the dog MC4R gene (1214 bp). In 120 Beagle dogs, two SNPs (A420C, C895T) were identiﬁed and their relation with body weight was analyzed with RFLP-PCR method. The results showed that the SNP at A420C was signiﬁcantly associated with canine body weight trait when it changed amino acid 101 of the MC4R protein from asparagine to threonine,while canine body weight variations were significant in female dogs when MC4R nonsense mutation at C895T. It suggested that the two SNPs might affect the MC4R gene’s function which was relative to body weight in Beagle dogs. Therefore, MC4R was a candidate gene for selecting different size dogs with the MC4R SNPs (A420C, C895T) being potentially valuable as a genetic marker.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

The SNPs of Melanocortin 4 Receptor (MC4R) Associated with Body Weight in Beagle Dogs

Zeng

Zhang

2014

Exp. Anim.

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“…The MC4R gene of the dog and red fox appeared to be less polymorphic and in both species 4 SNPs were found, including 1 missense substitution in the dog (c.637G 1 T, 213Val 1 Phe) [Skorczyk et al, 2007]. This missense SNP was analyzed in terms of morphological traits of Golden Retrievers, but no association was found [van den Berg et al, 2010]. Our study showed a comparative chromosome localization of 2 important candidate genes (FTO and INSIG2) for fat accumulation and their polymorphism for the first time.…”

Section: Discussionmentioning

confidence: 96%

Two Candidate Genes (FTO and INSIG2) for Fat Accumulation in Four Canids: Chromosome Mapping, Gene Polymorphisms and Association Studies of Body and Skin Weight of Red Foxes

Grzes¹,

Szczerbal²,

Fijak-Nowak³

et al. 2011

Cytogenet Genome Res

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Fat accumulation is a polygenic trait which has a significant impact on human health and animal production. Obesity is also an increasingly serious problem in dog breeding. The FTO and INSIG2 are considered as candidate genes associated with predisposition for human obesity. In this report we present a comparative genomic analysis of these 2 genes in 4 species belonging to the family Canidae – the dog and 3 species which are kept in captivity for fur production, i.e. red fox, arctic fox and Chinese raccoon dog. We cytogenetically mapped these 2 loci by FISH and compared the entire coding sequence of INSIG2 and a fragment of the coding sequence of FTO. The FTO gene was assigned to the following chromosomes: CFA2q25 (dog), VVU2q21 (red fox), ALA8q25 (arctic fox) and NPP10q24–25 (Chinese raccoon dog), while the INSIG2 was mapped to CFA19q17, VVU5p14, ALA24q15 and NPP9q22, respectively. Altogether, 29 SNPs were identified (16 in INSIG2 and 13 in FTO) and among them 2 were missense substitutions in the dog (23C/T, Thr>Met in the FTO gene and 40C/A, Arg>Ser in INSIG2). The distribution of these 2 SNPs was studied in 14 dog breeds. Two synonymous SNPs, one in the FTO gene (–28T>C in the 5′-flanking region) and one in the INSIG2 (10175C>T in intron 2), were used for the association studies in red foxes (n = 390) and suggestive evidence was observed for their association with body weight (FTO, p < 0.08) and weight of raw skin (INSIG2, p < 0.05). These associations indicate that both genes are potential candidates for growth or adipose tissue accumulation in canids. We also suggest that the 2 missense substitutions found in dogs should be studied in terms of genetic predisposition to obesity.

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“…It was suggested that the variant might be functioning normally because both valine and phenylalanine are hydrophobic [17]. This variant was identified in another more recent study [18]. In preliminary analysis of 187 Golden Retrievers, no association between the polymorphisms and morphological measures were found.…”

Section: Introductionmentioning

confidence: 99%

“…However, these authors suggested that the variant will likely affect receptor function, because this missense variant changed an amino acid residue that is highly conserved and under strong purifying selection. Furthermore, PolyPen program predicted that this polymorphism is likely damaging, although the authors conceded that this prediction needed to be experimentally verified by in vitro assays [18]. …”

Section: Introductionmentioning

confidence: 99%

Pharmacological characterization of canine melancortin-4 receptor and its natural variant V213F

Jin

Tao

2011

Domestic Animal Endocrinology

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Dogs have become one of most important companion animals in the modern society. However, it is estimated that 20–40% of owned dogs are obese suggesting that obesity has become one of the most important canine health problem. In addition, obesity in dogs also leads to type II diabetes. Since the melanocortin-4 receptor (MC4R) has been demonstrated to be essential in maintaining energy homeostasis in several different species, including rodents and human, we initiated studies towards elucidating the roles of MC4R in obesity pathogenesis in dogs. Recently, canine MC4R was cloned and a missense variant V213F was identified. We designed primers and successfully cloned canine MC4R and generated the variant V213F by site-directed mutagenesis. The objective of this study was to investigate the pharmacological properties of canine MC4R and its natural variant V213F. We measured ligand binding and signaling properties using both natural and synthetic ligands. Human MC4R was also included in the experiments for comparison. Both wild type canine MC4R and its natural variant V213F functioned normally in terms of binding and signaling. Of the ligands we used, [Nle4, D-Phe7]-α-melanocyte stimulating hormone is the most potent ligand. We conclude that the cloned canine MC4R is a functional receptor and the natural variant V213F does not have any functional defect and therefore is not likely to cause obesity in dogs.

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Analysis of variation in the melanocortin‐4 receptor gene (mc4r) in golden retriever dogs

Cited by 20 publications

References 6 publications

The SNPs of Melanocortin 4 Receptor (<i>MC4R</i>) Associated with Body Weight in Beagle Dogs

The SNPs of Melanocortin 4 Receptor (<i>MC4R</i>) Associated with Body Weight in Beagle Dogs

Two Candidate Genes <i>(FTO</i> and <i>INSIG2)</i> for Fat Accumulation in Four Canids: Chromosome Mapping, Gene Polymorphisms and Association Studies of Body and Skin Weight of Red Foxes

Pharmacological characterization of canine melancortin-4 receptor and its natural variant V213F

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